The molecular basis for inhibition of sulindac and its metabolites towards human aldose reductase.

Article Details

Citation

Copy to clipboard

Zheng X, Zhang L, Zhai J, Chen Y, Luo H, Hu X

The molecular basis for inhibition of sulindac and its metabolites towards human aldose reductase.

FEBS Lett. 2012 Jan 2;586(1):55-9. doi: 10.1016/j.febslet.2011.11.023. Epub 2011 Dec 8.

PubMed ID

22155003 [ View in PubMed

]

Abstract

Sulindac (SLD) exhibits both the highest inhibitory activity towards human aldose reductase (AR) among popular non-steroidal anti-inflammatory drugs and clear beneficial clinical effects on Type 2 diabetes. However, the molecular basis for these properties is unclear. Here, we report that SLD and its pharmacologically active/inactive metabolites, SLD sulfide and SLD sulfone, are equally effective as un-competitive inhibitors of AR in vitro. Crystallographic analysis reveals that pi-pi stacking favored by the distinct scaffold of SLDs is pivotal to their high AR inhibitory activities. These results also suggest that SLD sulfone could be a potent lead compound for AR inhibition in vivo.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Exisulind	Aldose reductase	Protein	Humans	Unknown	Inhibitor	Details